The technique of human cell culture will be employed to explore purine and pyrimidine metabolism. The proposed studies include a search for natural intermediates that influence the velocity of purine and pyrimidine synthesis, and a search for isozymes in different mammalian tissues. The catabolism of uracil and thymine will also be studied. A second project is devoted to exploring the role of natural pyrimidines and pyrimidine-like molecules in the functioning of the brain. Finally, a program is proposed for the isolation and characterization of mutants isolated from populations of Friend erythroleukemic cells. BIBLIOGRAPHIC REFERENCES: Krooth, R.S. (1976). Genes, behavior, and what will become of us? Man and Medicine (in press). Krooth, R.S., Hsiao, W.L., Lam, G., and Potvin, B. (1976). Effect of growing human fibroblasts in 6-azauridine on the specific activity for enzymes involved in the synthesis of uridine-5'-monophosphate. In: Calabresi, P. and McDonald, C.J. (Editors). Azaribine. A Symposium on Triacetyl-6-azauridine. (In press).